Human MCTS1-dependent translation of JAK2 is essential for IFN-γ immunity to mycobacteria.

Human inherited disorders of interferon-gamma (IFN-γ) immunity underlie severe mycobacterial diseases. We report X-linked recessive MCTS1 deficiency in men with mycobacterial disease from kindreds of different ancestries (from China, Finland, Iran, and Saudi Arabia). Complete deficiency of this translation re-initiation factor impairs the translation of a subset of proteins, including the kinase JAK2 in all cell types tested, including T lymphocytes and phagocytes. JAK2 expression is sufficiently low to impair cellular responses to interleukin-23 (IL-23) and partially IL-12, but not other JAK2-dependent cytokines. Defective responses to IL-23 preferentially impair the production of IFN-γ by innate-like adaptive mucosal-associated invariant T cells (MAIT) and γδ T lymphocytes upon mycobacterial challenge. Surprisingly, the lack of MCTS1-dependent translation re-initiation and ribosome recycling seems to be otherwise physiologically redundant in these patients. These findings suggest that X-linked recessive human MCTS1 deficiency underlies isolated mycobacterial disease by impairing JAK2 translation in innate-like adaptive T lymphocytes, thereby impairing the IL-23-dependent induction of IFN-γ.

A-series agent A-234: initial in vitro and in vivo characterization.

A-series agent A-234 belongs to a new generation of nerve agents. The poisoning of a former Russian spy Sergei Skripal and his daughter in Salisbury, England, in March 2018 led to the inclusion of A-234 and other A-series agents into the Chemical Weapons Convention. Even though five years have already passed, there is still very little information on its chemical properties, biological activities, and treatment options with established antidotes. In this article, we first assessed A-234 stability in neutral pH for subsequent experiments. Then, we determined its inhibitory potential towards human recombinant acetylcholinesterase (HssAChE; EC 3.1.1.7) and butyrylcholinesterase (HssBChE; EC 3.1.1.8), the ability of HI-6, obidoxime, pralidoxime, methoxime, and trimedoxime to reactivate inhibited cholinesterases (ChEs), its toxicity in rats and therapeutic effects of different antidotal approaches. Finally, we utilized molecular dynamics to explain our findings. The results of spontaneous A-234 hydrolysis showed a slow process with a reaction rate displaying a triphasic course during the first 72 h (the residual concentration 86.2%). A-234 was found to be a potent inhibitor of both human ChEs (HssAChE IC50 = 0.101 ± 0.003 µM and HssBChE IC50 = 0.036 ± 0.002 µM), whereas the five marketed oximes have negligible reactivation ability toward A-234-inhibited HssAChE and HssBChE. The acute toxicity of A-234 is comparable to that of VX and in the context of therapy, atropine and diazepam effectively mitigate A-234 lethality. Even though oxime administration may induce minor improvements, selected oximes (HI-6 and methoxime) do not reactivate ChEs in vivo. Molecular dynamics implies that all marketed oximes are weak nucleophiles, which may explain the failure to reactivate the A-234 phosphorus-serine oxygen bond characterized by low partial charge, in particular, HI-6 and trimedoxime oxime oxygen may not be able to effectively approach the A-234 phosphorus, while pralidoxime displayed low interaction energy. This study is the first to provide essential experimental preclinical data on the A-234 compound.

Physiologically relevant fluorescent assay for identification of 17ß-hydroxysteroid dehydrogenase type 10 inhibitors.

Mitochondrial enzyme 17ß-hydroxysteroid dehydrogenase type 10 (HSD10) is a potential molecular target for treatment of mitochondrial-related disorders such as Alzheimer's disease (AD). Its over-expression in AD brains is one of the critical factors disturbing the homeostasis of neuroprotective steroids and exacerbating amyloid beta (Aß)-mediated mitochondrial toxicity and neuronal stress. This study was focused on revalidation of the most potent HSD10 inhibitors derived from benzothiazolyl urea scaffold using fluorescent-based enzymatic assay with physiologically relevant substrates of 17ß-oestradiol and allopregnanolone. The oestradiol-based assay led to the identification of two nanomolar inhibitors (IC50 70 and 346 nM) differing from HSD10 hits revealed from the formerly used assay. Both identified inhibitors were found to be effective also in allopregnanolone-based assay with non-competitive or uncompetitive mode of action. In addition, both inhibitors were confirmed to penetrate the HEK293 cells and they were able to inhibit the HSD10 enzyme in the cellular environment. Both molecules seem to be potential lead structures for further research and development of HDS10 inhibitors.

Randomized evaluation of decision support interventions for atrial fibrillation: Rationale and design of the RED-AF study.

BACKGROUND: Shared decision making (SDM) improves the likelihood that patients will receive care in a manner consistent with their priorities. To facilitate SDM, decision aids (DA) are commonly used, both to prepare a patient before their clinician visit, as well as to facilitate discussion during the visit. However, the relative efficacy of patient-focused or encounter-based DAs on SDM and patient outcomes remains largely unknown. We aim to directly estimate the comparative effectiveness of two DA's on SDM observed in encounters to discuss stroke prevention strategies in patients with atrial fibrillation (AF). METHODS: The study aims to recruit 1200 adult patients with non-valvular AF who qualify for anticoagulation therapy, and their clinicians who manage stroke prevention strategies, in a 2x2 cluster randomized multi-center trial at six sites. Two DA's were developed as interactive, online, non-linear tools: a patient decision aid (PDA) to be used by patients before the encounter, and an encounter decision aid (EDA) to be used by clinicians with their patients during the encounter. Patients will be randomized to PDA or usual care; clinicians will be randomized to EDA or usual care. RESULTS: Primary outcomes are quality of SDM, patient decision making, and patient knowledge. Secondary outcomes include anticoagulation choice, adherence, and clinical events. CONCLUSION: This trial is the first randomized, head-to-head comparison of the effects of an EDA versus a PDA on SDM. Our results will help to inform future SDM interventions to improve patients' AF outcomes and experiences with stroke prevention strategies.

Charged pyridinium oximes with thiocarboxamide moiety are equally or less effective reactivators of organophosphate-inhibited cholinesterases compared to analogous carboxamides.

The organophosphorus antidotes, so-called oximes, are able to restore the enzymatic function of acetylcholinesterase (AChE) or butyrylcholinesterase (BChE) via cleavage of organophosphate from the active site of the phosphylated enzyme. In this work, the charged pyridinium oximes containing thiocarboxamide moiety were designed, prepared and tested. Their stability and pKa properties were found to be analogous to parent carboxamides (K027, K048 and K203). The inhibitory ability of thiocarboxamides was found in low µM levels for AChE and high µM levels for BChE. Their reactivation properties were screened on human recombinant AChE and BChE inhibited by nerve agent surrogates and paraoxon. One thiocarboxamide was able to effectively restore function of NEMP- and NEDPA-AChE, whereas two thiocarboxamides were able to reactivate BChE inhibited by all tested organophosphates. These results were confirmed by reactivation kinetics, where thiocarboxamides were proved to be effective, but less potent reactivators if compared to carboxamides.

E4 Transfer (E=P, As) to Ni Complexes.

The use of [Cp''2 Zr(η1:1 -E4 )] (E=P (1 a), As (1 b), Cp''=1,3-di-tert-butyl-cyclopentadienyl) as phosphorus or arsenic source, respectively, gives access to novel stable polypnictogen transition metal complexes at ambient temperatures. The reaction of 1 a/1 b with [CpR NiBr]2 (CpR =CpBn (1,2,3,4,5-pentabenzyl-cyclopentadienyl), Cp''' (1,2,4-tri-tert-butyl-cyclopentadienyl)) was studied, to yield novel complexes depending on steric effects and stoichiometric ratios. Besides the transfer of the complete En unit, a degradation as well as aggregation can be observed. Thus, the prismane derivatives [(Cp'''Ni)2 (µ,η3:3 -E4 )] (2 a (E=P); 2 b (E=As)) or the arsenic containing cubane [(Cp'''Ni)3 (µ3 -As)(As4 )] (5) are formed. Furthermore, the bromine bridged cubanes of the type [(CpR Ni)3 {Ni(µ-Br)}(µ3 -E)4 ]2 (CpR =Cp''': 6 a (E=P), 6 b (E=As), CpR =CpBn : 8 a (E=P), 8 b (E=As)) can be isolated. Here, a stepwise transfer of En units is possible, with a cyclo-E4 2- ligand being introduced and unprecedented triple-decker compounds of the type [{(CpR Ni)3 Ni(µ3 -E)4 }2 (µ,η4:4 -E'4 )] (CpR =CpBn , Cp'''; E/E'=P, As) are obtained.

Derivatives of montanine-type alkaloids and their implication for the treatment of Alzheimer's disease: Synthesis, biological activity and in silico study.

Alzheimers disease (AD) is the most common neurodegenerative disorder, characterized by neuronal loss and cognitive impairment. Currently, very few drugs are available for AD treatment, and a search for new therapeutics is urgently needed. Thus, in the current study, twenty-eight new derivatives of montanine-type Amaryllidaceae alkaloids were synthesized and evaluated for their ability to inhibit human recombinant acetylcholinesterase (hAChE) and butyrylcholinesterase (hBuChE). Three derivatives (1n, 1o, and 1p) with different substitution patterns demonstrated significant selective inhibitory potency for hAChE (IC50 < 5 µM), and one analog, 1v, showed selective hBuChE inhibition activity (IC50 = 1.73 ± 0.05 µM). The prediction of CNS availability, as disclosed by the BBB score, suggests that the active compounds in this survey should be able pass through the blood-brain barrier (BBB). Cytotoxicity screening and docking studies were carried out for the two most pronounced cholinesterase inhibitors, 1n and 1v.

Pyridinium-2-carbaldoximes with quinolinium carboxamide moiety are simultaneous reactivators of acetylcholinesterase and butyrylcholinesterase inhibited by nerve agent surrogates.

The pyridinium-2-carbaldoximes with quinolinium carboxamide moiety were designed and synthesised as cholinesterase reactivators. The prepared compounds showed intermediate-to-high inhibition of both cholinesterases when compared to standard oximes. Their reactivation ability was evaluated in vitro on human recombinant acetylcholinesterase (hrAChE) and human recombinant butyrylcholinesterase (hrBChE) inhibited by nerve agent surrogates (NIMP, NEMP, and NEDPA) or paraoxon. In the reactivation screening, one compound was able to reactivate hrAChE inhibited by all used organophosphates and two novel compounds were able to reactivate NIMP/NEMP-hrBChE. The reactivation kinetics revealed compound 11 that proved to be excellent reactivator of paraoxon-hrAChE better to obidoxime and showed increased reactivation of NIMP/NEMP-hrBChE, although worse to obidoxime. The molecular interactions of studied reactivators were further identified by in silico calculations. Molecular modelling results revealed the importance of creation of the pre-reactivation complex that could lead to better reactivation of both cholinesterases together with reducing particular interactions for lower intrinsic inhibition by the oxime.

Amaryllidaceae Alkaloids of Norbelladine-Type as Inspiration for Development of Highly Selective Butyrylcholinesterase Inhibitors: Synthesis, Biological Activity Evaluation, and Docking Studies.

Alzheimer's disease (AD) is a multifactorial neurodegenerative condition of the central nervous system (CNS) that is currently treated by cholinesterase inhibitors and the N-methyl-d-aspartate receptor antagonist, memantine. Emerging evidence strongly supports the relevance of targeting butyrylcholinesterase (BuChE) in the more advanced stages of AD. Within this study, we have generated a pilot series of compounds (1-20) structurally inspired from belladine-type Amaryllidaceae alkaloids, namely carltonine A and B, and evaluated their acetylcholinesterase (AChE) and BuChE inhibition properties. Some of the compounds exhibited intriguing inhibition activity for human BuChE (hBuChE), with a preference for BuChE over AChE. Seven compounds were found to possess a hBuChE inhibition profile, with IC50 values below 1 µM. The most potent one, compound 6, showed nanomolar range activity with an IC50 value of 72 nM and an excellent selectivity pattern over AChE, reaching a selectivity index of almost 1400. Compound 6 was further studied by enzyme kinetics, along with in-silico techniques, to reveal the mode of inhibition. The prediction of CNS availability estimates that all the compounds in this survey can pass through the blood-brain barrier (BBB), as disclosed by the BBB score.

RNase T1 Refolding Assay for Determining Mitochondrial Cyclophilin D Activity: A Novel In Vitro Method Applicable in Drug Research and Discovery.

Human cyclophilin D is a mitochondrial peptidyl-prolyl isomerase that plays a role in regulating the opening of the mitochondrial permeability transition pore. It is considered a viable and promising molecular target for the treatment of diseases for which disease development is associated with pore opening, e.g., Alzheimer's disease or ischemia/reperfusion injury. Currently available and widely used in vitro methods based on Kofron's assay for determining cyclophilin D activity suffer from serious drawbacks and limitations. In this study, a completely novel approach for an in vitro assay of cyclophilin D activity using RNase T1 refolding is introduced. The method is simple and is more in line with the presumed physiological role of cyclophilin D in protein folding than Kofron's assay, which relies on a peptide substrate. The method is applicable for identifying novel inhibitors of cyclophilin D as potential drugs for the treatment of the diseases mentioned above. Moreover, the description of CypD activity in the in vitro RNase T1 refolding assay reveals new possibilities for investigating the role of cyclophilin D in protein folding in cells and may lead to a better understanding of its pathological and physiological roles.

Friend or enemy? Review of 17ß-HSD10 and its role in human health or disease.

17ß-hydroxysteroid dehydrogenase (17ß-HSD10) is a multifunctional human enzyme with important roles both as a structural component and also as a catalyst of many metabolic pathways. This mitochondrial enzyme has important functions in the metabolism, development and aging of the neural system, where it is involved in the homeostasis of neurosteroids, especially in regard to estradiol, changes in which make it an essential part of neurodegenerative pathology. These roles therefore, indicate that 17ß-HSD10 may be a possible druggable target for neurodegenerative diseases including Alzheimer's disease (AD), and in hormone-dependent cancer. The objective of this review was to provide a summary about physiological functions and pathological roles of 17ß-HSD10 and the modulators of its activity.

Acetylcholinesterase Inhibition of Diversely Functionalized Quinolinones for Alzheimer's Disease Therapy.

In this communication, we report the synthesis and cholinesterase (ChE)/monoamine oxidase (MAO) inhibition of 19 quinolinones (QN1-19) and 13 dihydroquinolinones (DQN1-13) designed as potential multitarget small molecules (MSM) for Alzheimer's disease therapy. Contrary to our expectations, none of them showed significant human recombinant MAO inhibition, but compounds QN8, QN9, and DQN7 displayed promising human recombinant acetylcholinesterase (hrAChE) and butyrylcholinesterase (hrBuChE) inhibition. In particular, molecule QN8 was found to be a potent and quite selective non-competitive inhibitor of hrAChE (IC50 = 0.29 µM), with Ki value in nanomolar range (79 nM). Pertinent docking analysis confirmed this result, suggesting that this ligand is an interesting hit for further investigation.

Benzothiazolyl Ureas are Low Micromolar and Uncompetitive Inhibitors of 17ß-HSD10 with Implications to Alzheimer's Disease Treatment.

Human 17ß-hydroxysteroid dehydrogenase type 10 is a multifunctional protein involved in many enzymatic and structural processes within mitochondria. This enzyme was suggested to be involved in several neurological diseases, e.g., mental retardation, Parkinson's disease, or Alzheimer's disease, in which it was shown to interact with the amyloid-beta peptide. We prepared approximately 60 new compounds based on a benzothiazolyl scaffold and evaluated their inhibitory ability and mechanism of action. The most potent inhibitors contained 3-chloro and 4-hydroxy substitution on the phenyl ring moiety, a small substituent at position 6 on the benzothiazole moiety, and the two moieties were connected via a urea linker (4at, 4bb, and 4bg). These compounds exhibited IC50 values of 1-2 µM and showed an uncompetitive mechanism of action with respect to the substrate, acetoacetyl-CoA. These uncompetitive benzothiazolyl inhibitors of 17ß-hydroxysteroid dehydrogenase type 10 are promising compounds for potential drugs for neurodegenerative diseases that warrant further research and development.

Novel Benzothiazole-based Ureas as 17ß-HSD10 Inhibitors, A Potential Alzheimer's Disease Treatment.

: It has long been established that mitochondrial dysfunction in Alzheimer's disease (AD) patients can trigger pathological changes in cell metabolism by altering metabolic enzymes such as the mitochondrial 17ß-hydroxysteroid dehydrogenase type 10 (17ß-HSD10), also known as amyloid-binding alcohol dehydrogenase (ABAD). We and others have shown that frentizole and riluzole derivatives can inhibit 17ß-HSD10 and that this inhibition is beneficial and holds therapeutic merit for the treatment of AD. Here we evaluate several novel series based on benzothiazolylurea scaffold evaluating key structural and activity relationships required for the inhibition of 17ß-HSD10. Results show that the most promising of these compounds have markedly increased potency on our previously published inhibitors, with the most promising exhibiting advantageous features like low cytotoxicity and target engagement in living cells.

Vector Control and Insecticidal Resistance in the African Malaria Mosquito Anopheles gambiae.

Mosquito-borne diseases (including malaria) belong among the leading causes of death in humans. Vector control is a crucial part of the global strategy for management of mosquito-associated diseases, when insecticide use is the most important component in this effort. However, drug and insecticide resistance threaten the successes made with existing methods. Reduction or elimination of malaria is not possible without effective mosquito control. This article reviews current strategies of intervention in vector control to decrease transmission of disease and covers current relevant knowledge in molecular biology, biochemistry, and medicinal chemistry.

Simultaneous determination of malondialdehyde and 3-nitrotyrosine in cultured human hepatoma cells by liquid chromatography-mass spectrometry.

Although reactive oxygen/nitrogen species (ROS/RNS) have a fundamental role in physiological processes, enhanced ROS/RNS production induced by exogenous sources, including drugs and other xenobiotics, may result in serious damage to biomolecules. Oxidative/nitrosative stress is being intensively investigated and might be responsible for a variety of health side effects. The present liquid chromatography-tandem mass spectrometry (LC-MS/MS) method provides reliable and accurate simultaneous measurement of malondialdehyde (MDA) and 3-nitrotyrosine (3-NT) in cultured human hepatoma (HepG2) cells. Sample preparation process involving ultrasonic homogenization, alkaline hydrolysis of protein-bound MDA and 3-NT, deproteination, derivatization of MDA by 2,4-dinitrophenylhydrazine and solid-phase extraction was optimized, ensuring the isolation and purification of desired analytes. Additionally, nonprotein thiols and nonprotein disulfides were measured using HPLC-UV. The established lower limit of quantification (0.025 nmol/mL for MDA; 0.0125 nmol/mL for 3-NT) allowed their LC-MS/MS determination in HepG2 cells exposed to model oxidizing agent, tert-butyl hydroperoxide (t-BOOH). The results show significant changes in MDA and 3-NT concentrations and alterations in thiol redox-state in dependence on the t-BOOH concentration and duration of its incubation in HepG2 cells. Concurrent evaluation of oxidative/nitrosative stress biomarkers in the in vitro model may significantly facilitate assessment of toxicity of newly developed drugs in preclinical trials and thus improve their safety profile.

Transfer Reagent for Bonding Isomers of Iron Complexes.

The cothermolysis of As4 and [Cp″2Zr(CO)2] (Cp″ = η5-C5H3tBu2) results in the formation of [Cp″2Zr(η1:1-As4)] (1) in high yields and the arsenic-rich complex [(Cp″2Zr)(Cp″Zr)(µ,η2:2:1-As5)] (2) as a minor product. In contrast to yellow arsenic, 1 is a light-stable, weighable and storable arsenic source for subsequent reactions. The transfer reaction of 1 with [Cp‴Fe(µ-Br)]2 (Cp‴ = η5-C5H2tBu3) yields the unprecedented bond isomeric complexes [(Cp‴Fe)2(µ,η4:4-As4)] (3a) and [(Cp‴Fe)2(µ,η4:4-cyclo-As4)] (3b). In contrast, the analogous reaction with the CpBn derivative [CpBnFe(µ-Br)]2 (CpBn = η5-C5(CH2(C6H5)5) leads exclusively to the triple decker complex [(CpBnFe)2(µ,η4:4-As4)] (4) possessing the tetraarsabutadiene-type ligand analogous to 3a. To elucidate the stability of the bonding isomers 3a and 3b, DFT calculations were performed. The oxidation of 4 with AgBF4 affords [(CpBnFe)2(µ,η5:5-As5)][BF4] (5), which is a product expanded by one arsenic atom, instead of the expected complex [(CpBnFe)2(µ,η4:4-cyclo-As4)]+.

Arsenic-Rich Polyarsenides Stabilized by Cp*Fe Fragments.

The redox chemistry of [Cp*Fe(η5 -As5 )] (1, Cp*=η5 -C5 Me5 ) has been investigated by cyclic voltammetry, revealing a redox behavior similar to that of its lighter congener [Cp*Fe(η5 -P5 )]. However, the subsequent chemical reduction of 1 by KH led to the formation of a mixture of novel Asn scaffolds with n up to 18 that are stabilized only by [Cp*Fe] fragments. These include the arsenic-poor triple-decker complex [K(dme)2 ][{Cp*Fe(µ,η2:2 -As2 )}2 ] (2) and the arsenic-rich complexes [K(dme)3 ]2 [(Cp*Fe)2 (µ,η4:4 -As10 )] (3), [K(dme)2 ]2 [(Cp*Fe)2 (µ,η2:2:2:2 -As14 )] (4), and [K(dme)3 ]2 [(Cp*Fe)4 (µ4 ,η4:3:3:2:2:1:1 -As18 )] (5). Compound 4 and the polyarsenide complex 5 are the largest anionic Asn ligand complexes reported thus far. Complexes 2-5 were characterized by single-crystal X-ray diffraction, 1 H NMR spectroscopy, EPR spectroscopy (2), and mass spectrometry. Furthermore, DFT calculations showed that the intermediate [Cp*Fe(η5 -As5 )]- , which is presumably formed first, undergoes fast dimerization to the dianion [(Cp*Fe)2 (µ,η4:4 -As10 )]2- .

Processing of double-R-loops in (CAG)·(CTG) and C9orf72 (GGGGCC)·(GGCCCC) repeats causes instability.

R-loops, transcriptionally-induced RNA:DNA hybrids, occurring at repeat tracts (CTG)n, (CAG)n, (CGG)n, (CCG)n and (GAA)n, are associated with diseases including myotonic dystrophy, Huntington's disease, fragile X and Friedreich's ataxia. Many of these repeats are bidirectionally transcribed, allowing for single- and double-R-loop configurations, where either or both DNA strands may be RNA-bound. R-loops can trigger repeat instability at (CTG)·(CAG) repeats, but the mechanism of this is unclear. We demonstrate R-loop-mediated instability through processing of R-loops by HeLa and human neuron-like cell extracts. Double-R-loops induced greater instability than single-R-loops. Pre-treatment with RNase H only partially suppressed instability, supporting a model in which R-loops directly generate instability by aberrant processing, or via slipped-DNA formation upon RNA removal and its subsequent aberrant processing. Slipped-DNAs were observed to form following removal of the RNA from R-loops. Since transcriptionally-induced R-loops can occur in the absence of DNA replication, R-loop processing may be a source of repeat instability in the brain. Double-R-loop formation and processing to instability was extended to the expanded C9orf72 (GGGGCC)·(GGCCCC) repeats, known to cause amyotrophic lateral sclerosis and frontotemporal dementia, providing the first suggestion through which these repeats may become unstable. These findings provide a mechanistic basis for R-loop-mediated instability at disease-associated repeats.

Complexes of monocationic Group 13 elements with pentaphospha- and pentaarsaferrocene.

Reactions of the sandwich complexes [Cp*Fe(η(5)-E5)] (Cp*=η(5)-C5Me5; E=P (1), As (2)) with the monovalent Group 13 metals Tl(+), In(+), and Ga(+) containing the weakly coordinating anion [TEF] ([TEF]=[Al{OC(CF3)3}4](-)) are described. Here, the one-dimensional coordination polymers [M(µ,η(5):η(1 -E5 FeCp*)3]n [TEF]n (E=P, M=Tl (3 a), In (3 b), Ga (3 c); E=As, M=Tl (4 a), In (4 b)) are obtained as sole products in good yields. All products were analyzed by single-crystal X-ray diffraction, revealing a similar assembly of the products with η(5)-bound E5 ligands and very weak σ-interactions between one P or As atom of the ring to the neighbored Group 13 metal cation. By exchanging the [TEF] anion of 4 a for the larger [FAl] anion ([FAl]=[FAl{OC6F10(C6F5)}3](-)), the coordination compound [Tl{(η(5)-As5)FeCp*}3][FAl] (5) without any σ-interactions of the As5-ring is obtained. All products are readily soluble in CH2 Cl2 and exhibit a dynamic coordination behavior in solution, which is supported by NMR spectroscopy and ESI-MS spectrometry as well as by osmometric molecular-weight determination. For a better understanding of the proceeding equilibrium DFT calculations of the cationic complexes were performed for the gas phase and in solution. Furthermore, the (31)P{(1)H} magic-angle spinning (MAS) NMR spectra of 3 a-c are presented and the first crystal structure of the starting material 2 was determined.